Bone may be the hardest, most durable substance in the body, but it’s not indestructible. There’s a thief at large – the disease osteoporosis–
slowly and silently draining bones away until they weaken or snap.
As life expectancy continues to climb, both women and men face the increased possibility of pain and disability caused by the insidious dis- ease, which causes bone to become porous and fragile, leading to an increased risk of fractures.
But women are much more likely to develop this condition during the time of menopause and the first years beyond as they lose more and more of the protective effect of natural estrogen, while men tend to lose more slowly, catching up with women by age 65 or 70.
“We’re living to be 10 years older than our parents and grandpar- ents,” says Gregory Mundy, M.D., the first John A. Oates Chair in Translational Medicine and director of the Vanderbilt Center in Bone Biology. “Many of us are going to live well into our 80s and 90s, and some of us longer.” As a result, he explains, many otherwise healthy adults face the very real possibility of being “crippled by their bones,”
a fate that Mundy and other researchers hope to avert by developing a better understanding of osteoporosis and new methods to prevent and treat it.
W R I T T E N B Y E L I Z A B E T H O L D E R I L L U S T R A T I O N B YG E T T Y I M A G E S
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The bones of an 89-year-old woman with osteoporosis, a disease in which bones become extremely porous.
The relationship between aging and increased bone fragility has long been recog- nized in medicine. But it was only in 1994 that a group of World Health Organization experts first quantified the criteria that defined osteoporosis as a disease.
“That was really a big impact on the field,” says S. Bobo Tanner, M.D., an assistant professor of Medicine in the Division of Rheumatology and the Division of Allergy and Immunology.
The number of people – particularly women – who are affected is significant: the National Osteoporosis Foundation (NOF) says some 10 million Americans – 80 per- cent of those female – are estimated to have osteoporosis, while another 34 million are considered at increased risk for developing the disease due to low bone mass.
Many people still think of osteoporo- sis as a benign condition that is an inevitable result of getting older. But statistics show that it should instead be viewed as a major health threat that is, in many cases, preventable.
MILLIONS SUFFER DISABILITY AND DEATH
Although osteoporosis can occur at any age, middle-aged females are particu- larly susceptible because they lose up to 20 percent of their bone mass in the first five to seven years after menopause. This bone density loss has been linked to the estrogen decline that occurs during and after menopause. While pain and loss of mobility often are associated with the condition, statistics published by the NOF show that many patients suffer much more serious outcomes:
• on average, nearly one-fourth of hip fracture patients 50 and over die in the first year after their injury, with mortality for men nearly twice that of women.
• one in five patients who were ambu- latory before a hip fracture requires long-term care afterwards, and the same percentage ends up in a nursing home.
• one in two women and one in four
men over 50 will suffer an osteoporo- sis-related fracture over their lifetime, and women who have one hip frac- ture are at greater risk of having a second one.
Besides the human toll the bone dis- ease takes, the NOF estimated the cost of care for osteoporosis-related fractures in 2002 at $18 billion annually and rising.
“It is a huge expense to look at the outcome we are trying to prevent, not to mention the mortality,” says Tanner. A hip replacement can cost up to $75,000, he explains, an amount that dwarfs the cost of preventive medication that might help prevent a hip fracture from occurring in the first place.
RESEARCH BRINGS TREATMENT ALTERNATIVES
Tanner says that perhaps 80 percent of bone health may be linked to the genes we’re born with, while the remaining 20 percent is influenced by lifestyle and other factors. Certain diseases and med- ications – steroids are one example – can cause bone loss in people of all ages.
Taking hormone replacement after menopause and calcium with vitamin D – which aids in absorption – were the earli- est treatments, but the drawbacks of both have been revealed by research studies over the years, while other medicines have been developed.
“Calcium plus D are not truly a treatment in and of themselves,” explains Tanner, although taking the supplements regularly has been linked to slower bone loss and, perhaps, fewer hip fractures.
Bones need an adequate supply of calcium to remain healthy, but taking the supple- ment doesn’t actually fix porous bone, Tanner explains.
And even though taking hormones for bone health has been shown to reduce frac- tures, the drugs are no longer recommended as a treatment since the large, randomized Women’s Health Initiative study linked them to a higher risk of breast cancer, heart attack and other threatening condi- tions in post-menopausal women.
The first drug approved in the United States specifically to treat osteo- porosis, a bisphosphonate branded as Fosamax, was approved by the Food and Drug Administration in 1995. Other types of bisphosphonates now include the brands Actonel, once-a-month Boniva, and the once-a-year medication Reclast.
These drugs are called anti-resorptives because they work by slowing or stopping the process of bone breakdown.
“You remodel about 10 percent of your skeleton each year,” explains Tanner, adding that people who do more weight- bearing exercise can remodel more. This lifelong process belies the idea of bone as a fixed organ; instead it goes through a constant process of breaking down and building back cells.
Other drugs that work similarly to the bisphosphonates are calcitonin and estrogen, which now are recommended to treat osteoporosis only in severe cases and if no other options are available.
Raloxifene – Evista is one – is a selec- tive estrogen receptor modulator (SERM) that has the added benefit of reducing low-density lipoprotein cholesterol as well as improving bone density.
And in 2002, the FDA approved the first osteoporosis treatment that actually stimulates new bone formation, a type of parathyroid hormone (PTH) called teri- paratide, sold under the brand name Forteo.
“It’s expensive and has to be taken by injection,” observes Mundy. “However, it works very well in people with severe bone loss.”
(80 PERCENT OF THEM WOMEN) HAVE OSTEOPOROSIS
10 million
Americans
All of these treatments have specific prescribing targets and carry with them the risk of a number of side effects, so patients should discuss the pros and cons of taking any of them with their doctor.
FUTURE HELP FROM A FAMILIAR MEDICINE?
An internationally renowned investi- gator in bone biology, Mundy is studying the use of statins – now widely prescribed in pill form to lower cholesterol – to speed the healing of tibia fractures, with an eye toward drawing additional funding for doing further research on using the familiar drug for broader bone health.
“We know that statins work well if they reach the bone,” Mundy explains.
In the pill form commonly taken to lower cholesterol, little of the medication gets beyond the liver to reach the bone.
Topical application to the skin seems to overcome that problem, Mundy says, as does injection locally at a fracture site, the delivery approach which will be used in his research study with lovastatin.
Other new drugs being studied are aimed at blocking the breakdown of bone and building bone back.
“The big need in osteoporosis is for a treatment that will restore bone that has been lost,” says Mundy, who is a profes- sor of Medicine in the Division of Clinical Pharmacology and also holds appointments in Pharmacology,
Orthopaedics and Cancer Biology. That action would better the effect of most current medications, which generally maintain the bone the way it is.
As the outsized baby-boom genera- tion ages, osteoporosis promises to become a bigger problem in the populace, a trend that already is reflected in the busy schedule of the Vanderbilt Osteoporosis Clinic, Tanner says. He would like to expand the clinic from the current two days a week to five to meet the anticipated demand.
Tanner says one concern in the field is the push at the federal level to cut the reim- bursement for the low-radiation dual-energy X-ray absorptiometry (DXA) scans that
have been the gold standard for diagnos- ing osteoporosis and evaluating the bene- fits of various treatments. Some physi- cian specialists are suggesting replacing the quick procedure that measures bone mineral density – which costs about $125 – with a CT scan that is four to five times more expensive and exposes the patient to much more radiation, Tanner says.
“It’s a bargain in comparison,” he says of the DXA test. Tanner fears testing for osteoporosis might decline if this effort succeeds, since many patients will resist traveling to a major medical center to get a CT scan and paying more when DXA scans often are available in the doctor’s office.
“Access to this test is going to disap- pear,” he says. “We have to keep access to bone density measurement available.”
In the future, Tanner thinks new imaging techniques may produce virtual bone biopsies that will foster a better understanding of the bone structure and the limitations and effects of current medications, which could enable more individualization of care.
“We may be able to target which medications are better for which people,”
he explains. VM
S. Bobo Tanner, M.D., left, and Gregory Mundy, M.D.
ANNE RAYNER
Although women reach their peak bone mass by about the age of 30, they can help maintain bone health by following these lifestyle and health care tips adapted from the National Osteoporosis Foundation.
■ get the recommended daily amounts of calcium and vitamin D – which aids in calcium absorption – preferably through food, but otherwise with supple- ments; adults 50 and older need 1,200 mg of calcium and 800 to 1,000 IU of vitamin D each day.
■ to promote the bone remodeling process do regular weight-bear- ing exercise, which could include walking, weight-training, dancing, jogging, stair-climbing, racquet sports or hiking.
■ avoid drinking excess alcohol and smoking.
■ talk to your health care provider regularly about your bone health.